Analysis of prognostic factors impacting oncologic outcomes after neoadjuvant tyrosine kinase inhibitor therapy for gastrointestinal stromal tumors

Brian K. Bednarski, Dejka M. Araujo, Min Yi, Keila E. Torres, Alexander Lazar, Jonathan Trent, Janice N. Cormier, Peter W T Pisters, Dina Chelouche Lev, Raphael E. Pollock, Barry W. Feig, Kelly K. Hunt

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background. Management of gastrointestinal stromal tumors (GISTs) has been transformed with tyrosine kinase inhibitors (TKIs). While data on optimal duration of adjuvant imatinib remains elusive, guidelines for administration of neoadjuvant TKIs remain unknown. Methods. Under an institutional review board-approved protocol, patients at our institution with a diagnosis of GIST treated with neoadjuvant TKIs and surgical resection were identified. Clinical and pathologic characteristics were obtained from medical records. Results. Ninety-three patients underwent surgical resection after neoadjuvant TKI therapy; 41 had primary and 52 had recurrent/metastatic GIST. Median follow-up was 2.4 years. Median duration of neoadjuvant therapy was 315 (range 3-1,611) days for primary and 537 (range 4-3,257) days for recurrent/metastatic GIST (p = 0.001). Two-year, recurrence-free survival (RFS) was 85 and 44 % for primary and recurrent/metastatic disease, respectively, whereas 2-year overall survival (OS) was 97 % for primary and 73 % for recurrent/metastatic GIST. For primary GIST, duration of neoadjuvant therapy >365 days (p = 0.02) was associated with higher risk of recurrence on univariate analysis, whereas none of the clinicopathologic factors impacted OS. For recurrent/metastatic disease, disease progression was associated with a shorter OS (p = 0.001), but no factors were found to impact RFS. Lastly, when examining all patients, KIT mutations (p = 0.03) and multivisceral resection (p = 0.011) predicted shorter RFS. Conclusions. Neoadjuvant TKIs can be effectively used for the treatment of primary and recurrent/metastatic GIST. While duration of neoadjuvant therapy, KIT mutation status, and the need for multivisceral resection can help to predict higher risk for recurrence, progression on neoadjuvant TKIs can aid in selection of patients with recurrent/metastatic disease for surgical resection.

Original languageEnglish
Pages (from-to)2499-2505
Number of pages7
JournalAnnals of Surgical Oncology
Volume21
Issue number8
DOIs
StatePublished - Jan 1 2014

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Gastrointestinal Stromal Tumors
Protein-Tyrosine Kinases
Neoadjuvant Therapy
Survival
Recurrence
Therapeutics
Mutation
Research Ethics Committees
Patient Selection
Medical Records
Disease Progression
Guidelines

ASJC Scopus subject areas

  • Surgery
  • Oncology

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Analysis of prognostic factors impacting oncologic outcomes after neoadjuvant tyrosine kinase inhibitor therapy for gastrointestinal stromal tumors. / Bednarski, Brian K.; Araujo, Dejka M.; Yi, Min; Torres, Keila E.; Lazar, Alexander; Trent, Jonathan; Cormier, Janice N.; Pisters, Peter W T; Lev, Dina Chelouche; Pollock, Raphael E.; Feig, Barry W.; Hunt, Kelly K.

In: Annals of Surgical Oncology, Vol. 21, No. 8, 01.01.2014, p. 2499-2505.

Research output: Contribution to journalArticle

Bednarski, BK, Araujo, DM, Yi, M, Torres, KE, Lazar, A, Trent, J, Cormier, JN, Pisters, PWT, Lev, DC, Pollock, RE, Feig, BW & Hunt, KK 2014, 'Analysis of prognostic factors impacting oncologic outcomes after neoadjuvant tyrosine kinase inhibitor therapy for gastrointestinal stromal tumors', Annals of Surgical Oncology, vol. 21, no. 8, pp. 2499-2505. https://doi.org/10.1245/s10434-014-3632-7
Bednarski, Brian K. ; Araujo, Dejka M. ; Yi, Min ; Torres, Keila E. ; Lazar, Alexander ; Trent, Jonathan ; Cormier, Janice N. ; Pisters, Peter W T ; Lev, Dina Chelouche ; Pollock, Raphael E. ; Feig, Barry W. ; Hunt, Kelly K. / Analysis of prognostic factors impacting oncologic outcomes after neoadjuvant tyrosine kinase inhibitor therapy for gastrointestinal stromal tumors. In: Annals of Surgical Oncology. 2014 ; Vol. 21, No. 8. pp. 2499-2505.
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abstract = "Background. Management of gastrointestinal stromal tumors (GISTs) has been transformed with tyrosine kinase inhibitors (TKIs). While data on optimal duration of adjuvant imatinib remains elusive, guidelines for administration of neoadjuvant TKIs remain unknown. Methods. Under an institutional review board-approved protocol, patients at our institution with a diagnosis of GIST treated with neoadjuvant TKIs and surgical resection were identified. Clinical and pathologic characteristics were obtained from medical records. Results. Ninety-three patients underwent surgical resection after neoadjuvant TKI therapy; 41 had primary and 52 had recurrent/metastatic GIST. Median follow-up was 2.4 years. Median duration of neoadjuvant therapy was 315 (range 3-1,611) days for primary and 537 (range 4-3,257) days for recurrent/metastatic GIST (p = 0.001). Two-year, recurrence-free survival (RFS) was 85 and 44 {\%} for primary and recurrent/metastatic disease, respectively, whereas 2-year overall survival (OS) was 97 {\%} for primary and 73 {\%} for recurrent/metastatic GIST. For primary GIST, duration of neoadjuvant therapy >365 days (p = 0.02) was associated with higher risk of recurrence on univariate analysis, whereas none of the clinicopathologic factors impacted OS. For recurrent/metastatic disease, disease progression was associated with a shorter OS (p = 0.001), but no factors were found to impact RFS. Lastly, when examining all patients, KIT mutations (p = 0.03) and multivisceral resection (p = 0.011) predicted shorter RFS. Conclusions. Neoadjuvant TKIs can be effectively used for the treatment of primary and recurrent/metastatic GIST. While duration of neoadjuvant therapy, KIT mutation status, and the need for multivisceral resection can help to predict higher risk for recurrence, progression on neoadjuvant TKIs can aid in selection of patients with recurrent/metastatic disease for surgical resection.",
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T1 - Analysis of prognostic factors impacting oncologic outcomes after neoadjuvant tyrosine kinase inhibitor therapy for gastrointestinal stromal tumors

AU - Bednarski, Brian K.

AU - Araujo, Dejka M.

AU - Yi, Min

AU - Torres, Keila E.

AU - Lazar, Alexander

AU - Trent, Jonathan

AU - Cormier, Janice N.

AU - Pisters, Peter W T

AU - Lev, Dina Chelouche

AU - Pollock, Raphael E.

AU - Feig, Barry W.

AU - Hunt, Kelly K.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background. Management of gastrointestinal stromal tumors (GISTs) has been transformed with tyrosine kinase inhibitors (TKIs). While data on optimal duration of adjuvant imatinib remains elusive, guidelines for administration of neoadjuvant TKIs remain unknown. Methods. Under an institutional review board-approved protocol, patients at our institution with a diagnosis of GIST treated with neoadjuvant TKIs and surgical resection were identified. Clinical and pathologic characteristics were obtained from medical records. Results. Ninety-three patients underwent surgical resection after neoadjuvant TKI therapy; 41 had primary and 52 had recurrent/metastatic GIST. Median follow-up was 2.4 years. Median duration of neoadjuvant therapy was 315 (range 3-1,611) days for primary and 537 (range 4-3,257) days for recurrent/metastatic GIST (p = 0.001). Two-year, recurrence-free survival (RFS) was 85 and 44 % for primary and recurrent/metastatic disease, respectively, whereas 2-year overall survival (OS) was 97 % for primary and 73 % for recurrent/metastatic GIST. For primary GIST, duration of neoadjuvant therapy >365 days (p = 0.02) was associated with higher risk of recurrence on univariate analysis, whereas none of the clinicopathologic factors impacted OS. For recurrent/metastatic disease, disease progression was associated with a shorter OS (p = 0.001), but no factors were found to impact RFS. Lastly, when examining all patients, KIT mutations (p = 0.03) and multivisceral resection (p = 0.011) predicted shorter RFS. Conclusions. Neoadjuvant TKIs can be effectively used for the treatment of primary and recurrent/metastatic GIST. While duration of neoadjuvant therapy, KIT mutation status, and the need for multivisceral resection can help to predict higher risk for recurrence, progression on neoadjuvant TKIs can aid in selection of patients with recurrent/metastatic disease for surgical resection.

AB - Background. Management of gastrointestinal stromal tumors (GISTs) has been transformed with tyrosine kinase inhibitors (TKIs). While data on optimal duration of adjuvant imatinib remains elusive, guidelines for administration of neoadjuvant TKIs remain unknown. Methods. Under an institutional review board-approved protocol, patients at our institution with a diagnosis of GIST treated with neoadjuvant TKIs and surgical resection were identified. Clinical and pathologic characteristics were obtained from medical records. Results. Ninety-three patients underwent surgical resection after neoadjuvant TKI therapy; 41 had primary and 52 had recurrent/metastatic GIST. Median follow-up was 2.4 years. Median duration of neoadjuvant therapy was 315 (range 3-1,611) days for primary and 537 (range 4-3,257) days for recurrent/metastatic GIST (p = 0.001). Two-year, recurrence-free survival (RFS) was 85 and 44 % for primary and recurrent/metastatic disease, respectively, whereas 2-year overall survival (OS) was 97 % for primary and 73 % for recurrent/metastatic GIST. For primary GIST, duration of neoadjuvant therapy >365 days (p = 0.02) was associated with higher risk of recurrence on univariate analysis, whereas none of the clinicopathologic factors impacted OS. For recurrent/metastatic disease, disease progression was associated with a shorter OS (p = 0.001), but no factors were found to impact RFS. Lastly, when examining all patients, KIT mutations (p = 0.03) and multivisceral resection (p = 0.011) predicted shorter RFS. Conclusions. Neoadjuvant TKIs can be effectively used for the treatment of primary and recurrent/metastatic GIST. While duration of neoadjuvant therapy, KIT mutation status, and the need for multivisceral resection can help to predict higher risk for recurrence, progression on neoadjuvant TKIs can aid in selection of patients with recurrent/metastatic disease for surgical resection.

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